{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:47:59Z","timestamp":1762508879185,"version":"3.37.3"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK107407","R01 DK115392"],"award-info":[{"award-number":["R01 DK107407","R01 DK115392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Human physiology and epidemiology studies have demonstrated complex interactions between the renin\u2013angiotensin\u2013aldosterone system, parathyroid hormone\u00a0and calcium homeostasis. Several of these studies have suggested that aldosterone inhibition may lower parathyroid hormone (PTH) levels. The objective of this study was to assess the effect of 4 weeks of maximally tolerated mineralocorticoid receptor antagonist therapy with eplerenone on PTH\u00a0levels in patients with primary hyperparathyroidism (P\u2010HPT) when compared to amiloride and placebo. We also investigated the synergistic effect of these interventions when combined with cinacalcet for an additional 2 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Randomized, double\u2010blinded, three parallel\u2010group, placebo\u2010controlled trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Patients with P\u2010HPT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Most patients were women (83%) and White (76%). Maximally tolerated doses of eplerenone and amiloride induced significant reductions in blood pressure and increases in renin and aldosterone production; however, despite these physiologic changes, neither intervention induced significant changes in PTH or calcium levels when compared to the placebo. Both eplerenone and amiloride therapy induced significant reductions in procollagen type 1 N\u2010terminal propeptide levels when compared to placebo. When cinacalcet therapy was added, PTH and calcium levels were markedly reduced in all groups; however, there was no significant difference in PTH or serum calcium reductions between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although maximally tolerated therapy with eplerenone and amiloride induced expected changes in renin, aldosterone\u00a0and blood pressure, there were no meaningful changes in PTH or serum calcium levels in P\u2010HPT patients. These results suggest that inhibition of aldosterone action does not have a clinically meaningful role in medical therapy for P\u2010HPT.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14840","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T04:29:44Z","timestamp":1667276984000},"page":"516-526","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the clinical and mechanistic effects of eplerenone and amiloride monotherapy, and combination therapy with cinacalcet, in primary hyperparathyroidism: A placebo\u2010controlled randomized trial"],"prefix":"10.1111","volume":"98","author":[{"given":"Wasita W.","family":"Parksook","sequence":"first","affiliation":[{"name":"Center for Adrenal Disorders, Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Endocrinology, Diabetes, and Hypertension Harvard Medical School  Boston Massachusetts USA"},{"name":"Brigham and 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